早产新生儿万古霉素血药谷浓度达标的影响因素研究

The factors affecting target attainment of vancomycin trough concentrations in preterm newborns

目的分析导致早产新生儿万古霉素血药谷浓度不达标或超标的影响因素,为临床用药提供参考。方法回顾性收集2016年12月—2021年3月接受万古霉素静脉治疗的早产新生儿血药谷浓度监测数据,根据《中国万古霉素治疗药物监测指南(2020更新版)》推荐,将万古霉素稳态谷浓度<5 mg/L的患儿纳入不达标组,5~15 mg/L的纳入达标组,>15 mg/L的纳入超标组。利用SPSS软件统计分析不同分组间临床特征差异,分析各因素对血药谷浓度达标情况的影响。结果82例早产新生儿中,万古霉素的中位谷浓度为12.50(7.95,18.05)mg/L。达标患儿47例,占57.32%,谷浓度中位数为10.90(7.80,13.30)mg/L;超标患儿27例,占32.93%,中位数为21.80(18.00,23.80)mg/L;不达标患儿仅8例,占9.75%,中位数为4.10(2.48,4.60)mg/L。单因素分析结果表明,不达标组与达标组患儿在矫正胎龄和当前体重方面,差异有统计学意义(P<0.05);超标组与达标组患儿在血肌酐值和给药间隔方面的差异具有统计学意义(P<0.01)。多因素logistic回归分析结果显示,血肌酐值(OR=1.063,95%CI:1.024~1.102,P=0.001,截断值:62μmol/L)和给药间隔(OR=6.693,95%CI:1.604~27.920,P=0.009)是导致万古霉素血药谷浓度超标的独立危险因素。结论在现行说明书给药方案下,仅有半数早产新生儿的血药谷浓度达到指南推荐范围,用药时应综合患儿矫正胎龄、当前体重、日剂量及血清肌酐值等情况,优化万古霉素给药方案,开展血药浓度监测以确保用药安全和有效。

Objective To examine the possible factors affecting the attainment of target serum trough concentration of vancomycin in premature newborns for optimization of clinical dosing regimens.Methods The vancomycin trough concentration data were collected retrospectively from preterm newborns who received intravenous infusion of vancomycin from December 2016 to March 2021.According to the Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin:2020 Update by the Division of Therapeutic Drug Monitoring,Chinese Pharmacological Society,the patients were assigned to failure(<5 mg/L)or success(5-15 mg/L)in target attainment,or beyond target group(>15 mg/L)base on vancomycin trough concentration.Statistical software SPSS was used to analyze differences in clinical characteristics between different groups,and profile various factors that may affect attainment of target serum trough concentration of vancomycin.Results The median(interquartile range)trough concentration of vancomycin was 12.50(7.95-18.05)mg/L in 82 preterm newborns.The target trough concentration of vancomycin was attained in 47 preterm newborns(57.32%),and the corresponding trough concentration of vancomycin was 10.90(7.80-13.30)mg/L.The trough concentration of vancomycin was beyond target in 27 preterm newborns(32.93%).The corresponding median trough concentration of vancomycin was 21.80(18.00-23.80)mg/L.Serum trough concentration of vancomycin failed to achieve the target in only 8 preterm newborns(9.75%).The corresponding median trough concentration was 4.10(2.48-4.60)mg/L.Univariate analysis showed that there were statistically significant differences(P<0.05)in postmenstrual age and current weight between the patients succeeded in attaining target trough concentration and those who failed to attain the target.Baseline serum creatinine and dosing interval showed statistically significant differences(P<0.01)between the newborns who attained the target concentration and those with higher trough concentration beyond the target.Multivariate regression analysis showed that baseline serum creatinine(OR=1.063,95%CI 1.024-1.102,P=0.001,cutoff:62μmol/L)and dosing interval(OR=6.693,95%CI 1.604-27.920,P=0.009)were independent risk factors for excessively high vancomycin trough concentrations.Conclusions The dosing regimens as recommended in the current package insert only enable the attainment of target serum trough concentration of vancomycin in half of the premature newborns.The dosing regimen of vancomycin should be optimized by taking postmenstrual age,current weight,baseline serum creatinine and dosing interval into account.Therapeutic drug monitoring is necessary to ensure safety and effectiveness.